Specialized Membrane Domains for Water Transport in Glial Cells: High-Resolution Immunogold Cytochemistry of Aquaporin-4 in Rat Brain

TLDR

Membrane water transport is essential for brain volume homeostasis and edema, and the rat AQP4 cDNA has recently been isolated. The study employed immunocytochemistry and high‑resolution immunogold electron microscopy to map AQP4‑mediated water flux in specific glial and ependymal membrane domains. AQP4 is highly polarized, abundant in glial membranes adjacent to capillaries, pia, subarachnoid space, ventricles, and osmosensory nuclei, and restricted to specific ependymal subpopulations, indicating specialized membrane domains that mediate water flow between glial cells, CSF cavities, and the intravascular space.

Abstract

Membrane water transport is critically involved in brain volume homeostasis and in the pathogenesis of brain edema. The cDNA encoding aquaporin-4 (AQP4) water channel protein was recently isolated from rat brain. We used immunocytochemistry and high-resolution immunogold electron microscopy to identify the cells and membrane domains that mediate water flux through AQP4. The AQP4 protein is abundant in glial cells bordering the subarachnoidal space, ventricles, and blood vessels. AQP4 is also abundant in osmosensory areas, including the supraoptic nucleus and subfornical organ. Immunogold analysis demonstrated that AQP4 is restricted to glial membranes and to subpopulations of ependymal cells. AQP4 is particularly strongly expressed in glial membranes that are in direct contact with capillaries and pia. The highly polarized AQP4 expression indicates that these cells are equipped with specific membrane domains that are specialized for water transport, thereby mediating the flow of water between glial cells and the cavities filled with CSF and the intravascular space.